This study evaluates the immune response to skin allografts placed in the anterior chamber of inbred rats that differ at various histocompatibility loci. Skin allografts of approximately 1 mm2 were placed into the anterior chamber of several strains of inbred rats (Brown Norway, Lewis, Fischer, and Buffalo) of varying degrees of histocompatibility differences. In the combinations where the histocompatibility differences were strong, the implants survived between 3-4 weeks and longer if weak histocompatibility differences were involved. Substantial evidence indicated that implant bearing animals became sensitized and rejected specific skin grafts in second set manner. Using the mixed lymphocyte reaction and non-complement mediated cellular cytotoxicity as in vitro assays of cell mediated immunity indicated that cellular mechanisms are involved in the rejection of the implants. The fact that anterior chamber implants survive for a longer period than comparable orthotopic skin grafts in spite of an environment that would normally result in the rejection is still a dilemma.